A mechanistic integrative computational model of macrophage polarization: Implications in human pathophysiology
Fig 3
IL-4-mediated signaling controls macrophage phenotype.
Comparison between model simulations and literature experimental data on IL-4 induced (A) STAT6 phosphorylation [65], (B-C) IRF-4 upregulation (time-course and at 24 h) [66, 67], (D) AKT activation [68], (E) PPARγ expression at 18 h [69, 70], (F-G) Arg-1 expression (time-course and at 24 h) [67, 71], (H) IL-10 secretion at 24 h [72], (I) VEGF secretion at 24 h [73], (J) downregulation of TNFα secretion at 24 h [72], and (K) HIF-2α stabilization (in response to IL-4 with or without hypoxia) [48]. (A-K) All literature data are measured in macrophage cell lines and values are for protein levels unless noted otherwise. Y-axes show normalized expression respectively (A, B, D, F: simulations and data are normalized to the maximum expression; C, G: normalized to the expression at 24 h post-treatment; E, H, I, J: normalized to the no-treatment/time 0 expression; K: normalized to the expression under IL-4 treatment with hypoxia). S–simulation, D–literature data, Utr–untreated, Trd–IL-4 treated, Hyp–hypoxia.